Identification of different mutational profiles in cancers arising in specific colon segments by next generation sequencing

Abstract

The objective of this study was to investigate the mutational profiles of cancers arising in different colon segments. To this aim, we have analyzed 37 colon cancer samples by use of the Ion AmpliSeq™ Comprehensive Cancer Panel. Overall, we have found 307 mutated genes, most of which already implicated in the development of colon cancer. Among these, 15 genes were mutated in tumors originating in all six colon segments and were defined “common genes” (i.e. APC, PIK3CA, TP53) whereas 13 genes were preferentially mutated in tumors originating only in specific colon segments and were defined “site-associated genes” (i.e. BLNK, PTPRD).In addition, the presence of mutations in 10 of the 307 identified mutated genes (NBN, SMUG1, ERBB2, PTPRT, EPHB1, ALK, PTPRD, AURKB, KDR and GPR124) were found to be of clinical relevance. Among clinically relevant genes, NBN and SMUG1 were identified as independent prognostic factors that predicted poor survival in colon cancer patients.In conclusion, the findings reported here indicate that tumors arising in different colon segments present differences in the type and/or frequency of genetic variants, with two of them being independent prognostic factors that predict poor survival in colon cancer patients.

Deep Next Generation Sequencing Identifies Somatic Mutational Signature in Egyptian Colorectal Cancer Patients

“…The frequency of those mutations increased from the colitis to nally the CRC, so they could be used as predictors for disease progression. Most of the above identi ed somatic mutations were observed mostly with the CRC [47], except for (c.640delT in ATM), (c.1621A > C in KIT), (c.2071G > A in RET) & (c.121delG in TP53) which were observed respectively in breast [57], soft tissues [58] & head and neck cancers [59]. This is the rst study to report their association with the colorectal carcinogenesis in Egyptian CRC patients.…”

“…The present study reported two somatic mutations with functional loss in FBXW7 gene (c.2001delG & c.4900A > G). These mutations were previously reported to be found mainly in the CRC patients [47,34]. Moreover, a recent study reported the presence of an association between the FBXW7 mutations and resistance to anti-epidermal growth factor receptor (EGFR) immunotherapy treatment that commonly used to manage metastatic CRC [48].…”

PTPRT and PTPRD Deleterious Mutations and Deletion Predict Bevacizumab Resistance in Metastatic Colorectal Cancer Patients

“…The association of rectal tumors with inferior PFS was surprising, considering that PFS in rectal tumor patients treated with bevacizumab and chemotherapy has been reported to be longer than for most other tumor sites [ 44 ]. Regarding tumor sites, it has further been reported that splenic flexure tumors have a high proportion of PTPRD mutations [ 45 ]. Although it is possible that patients with specific tumor locations are more likely to harbor PTPRD mutations and could be more likely to be bevacizumab resistant, our cohort only included two patients with splenic flexure tumors, and was therefore not suitable to confirm those results.…”

The Multiple Cellular Roles of SMUG1 in Genome Maintenance and Cancer

“…To this end, high expression of SMUG1 is associated with favorable prognosis in ovarian cancer [ 47 ]. Additionally, low SMUG1 expression and mutations in SMUG1 are associated with poor prognosis in breast and colon cancer, respectively [ 48 , 49 ]. Abdel-Fatah and colleagues looked at SMUG1 mRNA or protein expression levels in triple negative breast cancer cells.…”